About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.7357C>T, p.(Arg2453Cys)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen ATM VCEP v1.5.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
PM2_supporting applies under the VCEP fallback rule: although the global gnomAD v4.1 allele frequency (0.00161%, 26/1,614,000 alleles) exceeds the primary threshold of ≤0.001%, the variant is observed at n=1 in a single subpopulation (East Asian, AC=1, AN=44,878), which meets the VCEP criterion that a single-allele subpopulation occurrence is sufficiently rare to warrant PM2_supporting.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework was evaluated deterministically with applied criteria: PM2 supporting; no rule matched the adjudicated criteria.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
26 / 1,614,000 alleles
gnomAD v4.1: 26 / 1,614,000 alleles. Recorded AF 1.6109e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19403e-05; MAF= 0.00119%, 3/251250 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.44484e-05; MAF= 0.00544%, 1/18366 alleles, homozygotes = 0); grpmax FAF= 2.92e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
11 reported laboratory submissions
11 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ATM, a kinase involved in the DNA damage response, is mutated in various solid and hematologic malignancies.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
5 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV104592374, n = 5 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen ATM VCEP v1.5.0, with the data and sources behind each one.
27 criteria with recorded statuses: 1 met · 10 not met · 0 not assessed · 16 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000051.4:c.7357C>T (p.Arg2453Cys) is a missense variant in ATM exon 50, observed at very low frequency in population databases (gnomAD v4.1: 26/1,614,000 alleles, AF = 0.00161%; gnomAD v2.1: 3/251,250 alleles, AF = 0.00119%).
The variant meets PM2_supporting per the ClinGen HBOP VCEP v1.5.0 fallback rule: although global gnomAD v4 frequency (0.00161%) exceeds the primary threshold of ≤0.001%, the variant is observed at n=1 in the East Asian subpopulation, which is sufficiently rare to warrant supporting-level evidence for pathogenicity.
No pathogenic or likely pathogenic missense comparator at p.Arg2453 has been established (PS1 not met). REVEL score of 0.457 does not meet the VCEP PP3 threshold (>0.7333) or the BP4 threshold (≤0.249). SpliceAI predicts no splicing impact (max delta = 0.00).
No variant-specific functional assay data (PS3/BS3) or segregation data (PP1) are available. The VCEP functional assay reference tables do not include this variant. The VCEP Suppl Table S1 (PMID 40580951) classifies the variant as 'Functional' with high confidence based on combined in silico scores, but computational predictions alone do not constitute experimental functional evidence sufficient for PS3.
The variant has been reported in ClinVar as Uncertain Significance by 11 clinical laboratories (ClinVar Variation ID: 230366). No expert panel classification has been assigned. No peer-reviewed publication was identified that directly mentions NM_000051.4:c.7357C>T.
The variant has been reported in COSMIC (COSV104592374, n=5) in somatic cancers, but this observation does not independently support germline pathogenicity classification under the HBOP VCEP framework.
Applying the ClinGen HBOP VCEP v1.5.0 final classification rules (Richards et al. 2015 combining criteria), only PM2_supporting is met, with no benign criteria met. This does not reach the threshold for Likely Pathogenic (requires ≥2 supporting + ≥1 moderate, or ≥3 moderate, etc.) nor Likely Benign (requires ≥2 supporting benign). The variant is classified as Uncertain Significance.
No criteria match.
Met · 1
PM2 SupportingPM2_supporting applies under the VCEP fallback rule: although the global gnomAD v4.1 allele frequency (0.00161%, 26/1,614,000 alleles) exceeds the primary threshold of ≤0.001%, the variant is observed at n=1 in a single subpopulation (East Asian, AC=1, AN=44,878), which meets the VCEP criterion that a single-allele subpopulation occurrence is sufficiently rare to warrant PM2_supporting. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: total AF = 0.00161% (26/1
- 614
- 000)
- exceeds 0.001% primary threshold
- East Asian subpopulation: n=1 allele (AC=1
- AN=44
- 878)
- meets VCEP fallback for PM2_supporting
- No homozygotes observed in any population
Sources
Not met · 10 · evaluated, threshold not reached
PS1 PS1 requires a known pathogenic missense variant at the same amino acid residue (p.Arg2453) with splicing ruled out for both. No pathogenic or likely pathogenic missense comparator at p.Arg2453 was identified in ClinVar, the VCEP supplementary tables, or the reviewed literature. Three alternate substitutions at p.Arg2453 (R2453S, R2453G) are listed in the VCEP Suppl Table S1 but none has an established pathogenic classification in ClinVar. Details ▾Hide ▴
Evidence considered
- No pathogenic/likely pathogenic missense comparator at p.Arg2453 in ClinVar
- c.7357C>A (R2453S) and c.7357C>G (R2453G) listed in VCEP Suppl Table S1 without pathogenic ClinVar classification
Sources
vcep_atm_ps1_1_5vcep_suppl_tables1_pmid_40580951
PS3 No variant-specific experimental functional assay data were identified for NM_000051.4:c.7357C>T. The VCEP functional assay reference tables (clingen_hbop_atm_supplementary_tables_1_and_2_v1.xlsx) do not list this variant in either the ATM kinase activity or radiosensitivity assay summaries. The VCEP PS3/BS3 specifications require demonstration of failure to rescue ATM-specific features (e.g., phosphorylation of ATM-specific targets) and/or radiosensitivity in a validated assay system. The VCEP Suppl Table S1 (PMID 40580951) classifies c.7357C>T as 'Functional' with high confidence based on combined in silico scores, but this is a computational prediction, not experimental functional evidence meeting the PS3 threshold. Details ▾Hide ▴
Evidence considered
- Not listed in VCEP ATM kinase activity assay table
- Not listed in VCEP ATM radiosensitivity assay table
- Suppl Table S1 classifies as 'Functional' (computational prediction only)
Still missing
- No experimental functional studies have been performed on this variant
Sources
vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1vcep_suppl_tables1_pmid_40580951
PS4 No case-control study data are available for NM_000051.4:c.7357C>T. The VCEP requires a case-control study with p-value ≤0.05 and OR/HR/RR ≥2 or lower 95% CI ≥1.5. No such study has reported on this specific variant. Large consortium studies (e.g., BCAC, PMID:33471991) and ATM-specific case-control efforts (e.g., PMID:21787400, PMID:28779002) did not include or report this variant. Details ▾Hide ▴
Evidence considered
- No case-control study identified for this variant
- Variant is rare (gnomAD v4 AF = 0.00161%) and underpowered for case-control analysis
Still missing
- Case-control data unavailable for this rare variant
Sources
PP1 No segregation data are available for NM_000051.4:c.7357C>T. The VCEP requires co-segregation in affected relatives with ataxia-telangiectasia (AR condition): ≥3 affected relatives for strong, 2 for moderate, or 1 for supporting. No published or ClinVar-submitted segregation evidence was identified for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data available
Still missing
- No family segregation studies have been reported
PP3 The VCEP missense PP3 threshold requires REVEL >0.7333. The REVEL score for NM_000051.4:c.7357C>T is 0.457, which does not meet this threshold. SpliceAI predicts no splicing impact (max delta = 0.00), so the splicing arm of PP3 also does not apply. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.457 (threshold >0.7333 not met)
- SpliceAI max delta = 0.00 (no predicted splicing impact)
Sources
revelspliceai ↗
BA1 The VCEP BA1 threshold requires a grpmax filtering allele frequency >0.5% in gnomAD v4. The grpmax FAF for NM_000051.4:c.7357C>T is 1.376e-05 (0.001376%), which is well below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 1.376e-05 (0.001376%)
- far below 0.5% threshold
Sources
BS1 The VCEP BS1 threshold requires a grpmax filtering allele frequency >0.05% in gnomAD v4. The grpmax FAF for NM_000051.4:c.7357C>T is 1.376e-05 (0.001376%), which is well below the BS1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 1.376e-05 (0.001376%)
- far below 0.05% threshold
Sources
BS3 No variant-specific experimental functional assay data demonstrating a benign effect (rescue of ATM-specific features and/or radiosensitivity) were identified. The VCEP functional assay reference tables do not list c.7357C>T. The VCEP Suppl Table S1 classifies the variant as 'Functional' (i.e., predicted damaging), which is inconsistent with a BS3 argument. Details ▾Hide ▴
Evidence considered
- No experimental rescue data available for this variant
- VCEP Suppl Table S1 classifies as 'Functional' (not benign)
Still missing
- No experimental functional studies have been performed on this variant
Sources
vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1vcep_suppl_tables1_pmid_40580951
BP2 No evidence of co-occurrence in trans with a pathogenic or likely pathogenic ATM variant in an unaffected individual aged ≥18 years was identified. The VCEP PM3/BP2 points-based table requires confirmation of phase or homozygosity for scoring. Details ▾Hide ▴
Evidence considered
- No co-occurrence data available
Still missing
- No phase-confirmed co-occurrence observations reported
BP4 The VCEP BP4 missense threshold requires REVEL ≤0.249. The REVEL score for NM_000051.4:c.7357C>T is 0.457, which exceeds this threshold. The splicing arm of BP4 (SpliceAI ≤0.1) is met (max delta = 0.00), but this sub-rule is specified for splicing/silent/intronic variants, not missense variants. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.457 (threshold ≤0.249 not met)
- SpliceAI max delta = 0.00 (met for splicing arm
- but variant is missense)
Sources
revelspliceai ↗
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is reserved for null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, single/multi-exon deletion). NM_000051.4:c.7357C>T is a missense variant (p.Arg2453Cys) and does not fall into any PVS1-eligible variant class per the ClinGen HBOP VCEP ATM PVS1 decision tree. Details ▾Hide ▴
Evidence considered
- Missense variant
- not a null variant
- SpliceAI max delta = 0.00
- no cryptic splicing predicted
Sources
vcep_atm_pvs1_1_5pvs1_variant_assessment
PS2 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM: informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PM1 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0: benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined at this time for ATM. Details ▾Hide ▴
Sources
PM5 N/AThe ClinGen HBOP VCEP v1.5.0 explicitly states: 'Do not use for missense changes: Multiple amino acid substitutions at the same residue can be pathogenic or benign and bioinformatic tools cannot yet confidently distinguish them.' NM_000051.4:c.7357C>T is a missense variant (p.Arg2453Cys). PM5 is restricted to frameshifting or truncating variants with PTCs upstream of p.Arg3047, and splice variants with PVS1_VS(RNA) applied. Details ▾Hide ▴
PM6 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM: informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PP2 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM. Details ▾Hide ▴
Sources
PP4 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM: breast cancer is a disease with multiple genetic etiologies and there are no features that readily distinguish hereditary from sporadic causes. For AR disease, this evidence is built into the PM3/BP2 table. Details ▾Hide ▴
Sources
PP5 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM. Details ▾Hide ▴
Sources
BS2 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM. Details ▾Hide ▴
Sources
BS4 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM. Details ▾Hide ▴
Sources
BP1 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM. Details ▾Hide ▴
Sources
BP3 VCEPSkipped per adjudication instructions: trivially not_applicable. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM. Details ▾Hide ▴
Sources
BP6 VCEPNot applicable per ClinGen HBOP VCEP v1.5.0 for ATM: this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BP7 N/ABP7 is applicable only to synonymous substitutions and deep intronic variants (further than +7 and -21 at donor and acceptor sites, respectively). NM_000051.4:c.7357C>T is a missense variant (p.Arg2453Cys) in exon 50 and does not meet the variant class criteria for BP7. Details ▾Hide ▴
PS5 N/APS5 is not included in the ONLY ASSESS list for this adjudication. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.7357C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Arg2453Cys)
- GRCh38
- chr11:108330263 C>T
- GRCh37
- chr11:108200990 C>T
- ClinVar
- 230366
- COSMIC
- COSV104592374
Gene diagram
Every interpreted variant in ATM, mapped onto the exon structure of NM_000051.4. Select a row to find it on the plot.
ATMNM_000051.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in ATM
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
26 / 1,614,000 alleles
AF 1.61e-05 · 0 homozygotes · FAF 1.38e-05
gnomAD v2.1
3 / 251,250 alleles
AF 1.19e-05 · 0 homozygotes · FAF 2.92e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.6e-05 · 26 / 1,614,000 alleles · 0 hom · FAF 1.4e-05
| East Asian1 / 44,878 | 2.2e-05 |
| European (non-Finnish)24 / 1,180,004 | 2e-05 |
| Remaining individuals1 / 62,486 | 1.6e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.2e-05 · 3 / 251,250 alleles · 0 hom · FAF 2.9e-06
| East Asian1 / 18,366 | 5.4e-05 |
| European (non-Finnish)2 / 113,584 | 1.8e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.6109e-05; MAF= 0.00161%, 26/1614000 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22826e-05; MAF= 0.00223%, 1/44878 alleles, homozygotes = 0); grpmax FAF= 1.376e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19403e-05; MAF= 0.00119%, 3/251250 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.44484e-05; MAF= 0.00544%, 1/18366 alleles, homozygotes = 0); grpmax FAF= 2.92e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.457
- BayesDel
- -0.245
How the predictions were used
PP3 The VCEP missense PP3 threshold requires REVEL >0.7333. The REVEL score for NM_000051.4:c.7357C>T is 0.457, which does not meet this threshold. SpliceAI predicts no splicing impact (max delta = 0.00), so the splicing arm of PP3 also does not apply. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.457 (threshold >0.7333 not met)
- SpliceAI max delta = 0.00 (no predicted splicing impact)
Sources
revelspliceai ↗
BP4 The VCEP BP4 missense threshold requires REVEL ≤0.249. The REVEL score for NM_000051.4:c.7357C>T is 0.457, which exceeds this threshold. The splicing arm of BP4 (SpliceAI ≤0.1) is met (max delta = 0.00), but this sub-rule is specified for splicing/silent/intronic variants, not missense variants. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.457 (threshold ≤0.249 not met)
- SpliceAI max delta = 0.00 (met for splicing arm
- but variant is missense)
Sources
revelspliceai ↗
BP7 N/ABP7 is applicable only to synonymous substitutions and deep intronic variants (further than +7 and -21 at donor and acceptor sites, respectively). NM_000051.4:c.7357C>T is a missense variant (p.Arg2453Cys) in exon 50 and does not meet the variant class criteria for BP7. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.457. BayesDel score = -0.245392.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 17623063 ↗Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence.Edvardsen H et al. · 2007Examined linkage disequilibrium patterns and SNP haplotypes in the ATM gene in Norwegian breast cancer patients and controls; investigated association with radiosensitivity and post-lumpectomy local recurrence. NM_000051.4:c.7357C>T was not identified in this paper.Does not name this variant
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PMID 21787400 ↗Rare variants in the ATM gene and risk of breast cancer.Goldgar DE et al. · 2011Investigated rare ATM missense variants in breast cancer risk through case-control analysis across multiple cohorts. The study identified several ATM missense variants with evidence of association with breast cancer but did not include NM_000051.4:c.7357C>T in its reported variant set.Does not name this variant
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for the interpretation of sequence variants. This methodological guideline establishes the classification framework but does not discuss any specific ATM variant including NM_000051.4:c.7357C>T.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Described a standardized rules-based DNA variant scoring system for pathogenicity assessments in Mendelian disorders, analyzing over 16,500 pathogenicity assessments on 11,894 variants from 338 genes. NM_000051.4:c.7357C>T was not among the variants assessed.Does not name this variant
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PMID 28779002 ↗Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.Decker B et al. · 2017Sequenced coding regions of ATM, CHEK2, PALB2, and XRCC2 in 13,087 breast cancer cases and 5,488 controls from East Anglia, UK, to characterize the contribution of rare protein-truncating variants to breast cancer risk. The study focused on protein-truncating variants and did not report NM_000051.4:c.7357C>T (a missense variant).Does not name this variant
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Perspective review discussing the emerging landscape of breast cancer susceptibility alleles, categorizing them into rare high-penetrance, rare moderate-penetrance, and common low-penetrance classes. General gene-level discussion of ATM as a moderate-penetrance breast cancer gene; no specific variant including NM_000051.4:c.7357C>T was discussed.Does not name this variant
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PMID 20301317 ↗Hereditary Ataxia Overview.Adam MP et al. · 1993GeneReviews overview of hereditary ataxias. General clinical and genetic description of ataxia-telangiectasia and ATM; no specific variant including NM_000051.4:c.7357C>T was discussed.Does not name this variant
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PMID 20301790 ↗Ataxia-Telangiectasia.Adam MP et al. · 1993GeneReviews clinical summary of ataxia-telangiectasia. General description of ATM-related disease, diagnosis, and management; no specific variant including NM_000051.4:c.7357C>T was discussed.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
26 / 1,614,000 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
11 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/639508985
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/230366/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108200990-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108330263-C-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108330263-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.7357…
- OncoKB ↗www.oncokb.org/gene/ATM/R2453C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122708165
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.6109e-05; MAF= 0.00161%, 26/1614000 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22826e-05; MAF= 0.00223%, 1/44878 alleles, homozygotes = 0); grpmax FAF= 1.376e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19403e-05; MAF= 0.00119%, 3/251250 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.44484e-05; MAF= 0.00544%, 1/18366 alleles, homozygotes = 0); grpmax FAF= 2.92e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (11 clinical laboratories). (ClinVarID = 230366)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.457. BayesDel score = -0.245392.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ATM, a kinase involved in the DNA damage response, is mutated in various solid and hematologic malignancies.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104592374, n = 5 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.